The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily elvitegravir (EVG) versus twice-daily raltegravir added to a background regimen (containing a fully-active ritonavir-boosted protease inhibitor [PI/r] and a second agent) in HIV-1 infected, antiretroviral treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of antiretroviral agents.

The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA-defined Time to Loss of Virologic Response (TLOVR) algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 400 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Virologic response at Week 48 (percentage of participants with HIV-1 RNA < 50 copies/mL) was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Virologic response at Week 96 (percentage of participants with HIV-1 RNA < 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the missing = failure method, where participants with missing data were considered as having failed to meet the criteria for evaluation.

Elvitegravir 85 mg or 150 mg tablet administered orally once daily with food; dose level is dependent on which ritonavir-boosted protease inhibitor (PI/r) is administered as part of the background regimen.

Due to known drug interactions, participants who are taking ritonavir-boosted atazanavir (ATV/r) or lopinavir/r (LPV/r) as part of their background regimen will receive elvitegravir at a lower dose (85 mg) if randomized to the Elvitegravir Arm.

The background regimen will be constructed by the investigator based on viral resistance testing. The fully active PI will be defined by phenotypic resistance analysis. For phenotypic susceptibility, fully active is defined as being below the lower clinical or biological cutoff. Participants are required to take their ritonavir dose based on the dosing schedule indicated in the prescribing information for the PI; no additional ritonavir is required to be taken with EVG. No other marketed PIs are allowed as part of the background regimen due to unknown drug interactions.

The second agent can be one nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), etravirine, maraviroc, or T-20. However, the second agent must not include an integrase inhibitor; the nonnucleoside reverse transcriptase inhibitors efavirenz, nevirapine, or delavirdine (due to unknown drug interactions); or the fixed-dose combination therapies Atripla® or Trizivir® (abacavir sulfate/lamivudine/zidovudine). The second agent may or may not be fully active (except in Spain, where participants have to receive a fully active second agent, as requested by the Spanish regulatory agency).

If the M184V/I reverse transcriptase (RT) mutation is present on the screening genotype report and an NRTI is used as the second agent, then either FTC or LAM may be added as a third agent in the background regimen to maintain the M184V/I mutation. In this situation only, the fixed-dose combination therapies Combivir®, Truvada®, or Epzicom/Kivexa® may be prescribed as the combined second and third agents of the background regimen.

After Week 96, participants will continue to take their blinded study drug and attend visits until treatment assignments are unblinded, at which point they will be given the option to participate in an open-label EVG extension phase of the study.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening

Documented resistance or at least six months experience prior to screening with two or more different classes of antiretroviral agents

Stable antiretroviral regimen for at least 30 days prior to screening: however, participants may discontinue the antiretroviral regimen after screening and remain off therapy until baseline at the discretion of the investigator

Eligible to receive one of the fully-active ritonavir-boosted-PIs, and an allowed second agent

Participation in any other clinical trial (except for the etravirine or maraviroc expanded access program), without prior approval from sponsor

Any other clinical condition or prior therapy that would make participants unsuitable for the study

Known hypersensitivity to study drug, metabolites or formulation excipients

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708162